Here, we describe the different genome editing tools, their application to develop therapeutic approaches to β-hemoglobinopathies and ongoing clinical trials using genome editing strategies.Primary immunodeficiencies (PID) are a growing list of unique disorders that result in a failure of the innate/adaptive immune systems to fully respond to disease or infection. PIDs are classified into five broad categories; B cell disorders, combined B and T cell disorders, phagocytic disorders, complement disorders, and disorders with recurrent fevers and inflammation. Many of these disorders, such as X-SCID, WAS, and CGD lead to early death in children if intervention is not implemented. At present, the predominant method of curative therapy remains an allogeneic transplant from a healthy donor, however many complications and limitations exist with his therapy such as availability of donors, graft vs host disease, graft rejection, and infection. More recently, gene therapy using viral based complementation vectors have successfully been implemented to functionally correct patient cells in an autologous transplant, but these methods carry significant risks, including insertional mutagenesis, and provide non-physiological gene expression. For these reasons, gene-editing reagents such as targeted nucleases, base editors (BE), and prime editors (PE) are being explored. The BE and PE tools, sometimes referred to as digital editors, are of very high interest as they provide both enhanced molecular specificity and do not rely on DNA repair pathways after DSBs to change individual base pairs or directly replace DNA sequences responsible for pathogenic phenotypes. With this in mind the purpose of this chapter is to highlight some of the most common PIDs found within the human population, discuss successes and shortcomings of previous intervention strategies, and highlight how the next generation of gene-editing tools may be deployed to directly repair the underlying genetic causes of this class of disease.Genome editing, particularly the use of CRISPR-Cas9-based methodologies, is revolutionizing biology through its impacts on research and the translation of these into applications in biomedicine. Somatic genome editing aimed at treating individuals with disease raises some significant ethical issues, but proposed heritable interventions, through the use of genome editing in gametes or embryos, raise a number of distinct social, ethical and political issues. This review will consider some proposed uses of heritable human genome editing (HHGE) and several of the objections to these that have been raised. Making sense of such proposed uses requires viewing HHGE as an assisted reproductive technology (ART) that, like preimplantation genetic testing (PGT) and mitochondrial replacement techniques (MRT), aims to prevent disease transmission during sexual reproduction, rather than acting as a therapy for an existing individual. Applications beyond the paradigm of disease prevention raise even more difficult scientific and ethical questions. Here, I will discuss various themes that are prominent in discussions of the science and ethics of HHGE, including impacts on human dignity and society, the language of HHGE used for public dialogue and the governance of HHGE.Lung cancer with EGFR mutation is rare in our country, with an estimated incidence of 7-10%. It is well known that, in this type of disease, specific inhibitors should be used, as they increase patient survival and therefore prognosis. https://www.selleckchem.com/products/epz005687.html So-called tumour heterogeneity, the possibility of various mutations concurring in the same tumour, is currently being debated. We present a case of a double mutation of EGFR and discuss treatment, management and possible implications.Pulmonary papillary adenoma (PA) is an unusual tumor with only 32 reported cases to date. We present a case of a 69-year-old man, a smoker from the age of 12, with a central mass in the pulmonary left lower lobe identified in a PET-CT scan. Microscopical analysis of the Fine Needle Aspiration (FNA) samples showed fragments of a tumor comprised of abundant papillary structures lined by a monolayer of cytologically bland columnar to cuboidal epithelial cells. The immunohistochemical stains were positive for CK7, TTF-1 and EMA in the epithelial cells, and negative for MYC. Based on the imaging tests, histological features and immunohistochemical profile, the tumor was diagnosed as pulmonary PA. The cytologic and histologic features of this rare entity are described in detail and the value of FNA as an essential presurgical diagnostic procedure is emphasized.Endometrial stromal sarcoma (ESS) is an uncommon mesenchymal tumor that accounts for less than 1% of all primary uterine malignancies and extrauterine endometrial stromal sarcoma (EESS) is even rarer. We report the case of a 75-year-old woman with an abdominal tumor and multiple peritoneal implants. Histological analysis of the surgical specimens showed bland cellularity resembling normal endometrial stroma. The diagnosis of a low-grade EESS was confirmed by immunophenotypic findings and demonstration of JAZF1 translocation. After extensive sampling, no evidence of endometriosis was found. Our case showed atypical aggressive behavior and we discuss the possible influence of the high mitotic count (8/10 HPFs) in some areas of the tumor, the multifocality of the abdominal implants and the postmenopausal status of the patient. The unusual clinical presentation and extrauterine location of such a rare tumor were challenging implying a wide range of differential diagnosis. The correlation of morphological, immunohistochemical and molecular findings was necessary to arrive at the correct diagnosis.We report the case of a 46-year-old woman who presented with a tumor on the left labium majus in the region of the Bartholin gland. Surgical excision revealed a mucinous adenocarcinoma of intestinal-type (CK20+, CDX-2+). Magnetic resonance imaging, computed tomography of the chest and abdomen and colonoscopy ruled out the presence of other tumors. A second immunohistochemical study showed negative results for GATA-3, mammaglobin and GCDFP-15. Molecular analysis revealed a mutation in exon 2 of the KRAS gene. We discuss its differential diagnosis and the importance of being aware of this unusual variant of a mucinous adenocarcinoma the Bartholin gland.